It is chemically similar to the compounds that can be synthesized from cathinone as found in the khat (cathulla edullis) plant of eastern Africa.

It comes in the form of tablets or a powder, which users can swallow, snort, inject or insert rectally, producing effects which are somewhat similar to those of MDMA, amphetamine, and cocaine.

Mephedrone was first synthesized in 1929, but did not become widely known until it was rediscovered in 2003. By 2007, it was reported to be available for sale on the internet, by 2008 law enforcement agencies had become aware of the compound, and by 2010 it had been reported in most of Europe, becoming particularly prevalent in the United Kingdom.

Chemistry

Mephedrone, or 4-methylmethcathinone, is a synthetic molecule of the cathinone family. Cathinones are structurally similar to amphetamines, they contain a phenethylamine core featuring a phenyl ring bound to an amino (NH2) group through an ethyl chain with an additional methyl substitution at Rα. Amphetamines and cathinones are alpha-methylated phenethylamines, cathinones contain an additional carbonyl group at R1. Mephedrone contains an additional methyl substitutions at RN, similarly to MDMA and methamphetamine, and R4 of its phenyl ring.

Pharmacology

Several articles published near the end of 2011 examined the effects of mephedrone in the brains of rats, as well as examining the reinforcing potential of mephedrone. Dopamine and serotonin were collected using microdialysis, and increases in dopamine and serotonin were measured. Mephedrone administration caused about a 500% increase in dopamine, and about a 950% increase in serotonin. They reached their peak concentrations at 40 minutes and 20 minutes and returned to baseline by 120 minutes after injection.

Analysis of the ratio for dopamine and serotonin indicated mephedrone was preferentially a serotoninreleaser, with a ratio of 1.22:1 (serotonin vs. dopamine). Additionally, half-lives for the decrease in dopamine and serotonin were calculated and found to have decay rates of 24.5 minutes and 25.5 minutes.

These findings show mephedrone induces a massive increase in both dopamine and serotonin, combined with rapid clearance. This increase in neurotransmitters provides an explanation for the euphoric and stimulating subjective effects induced by this experience. The rapid rise and subsequent fall of dopamine levels could also explain some of the addictive properties of mephedrone display in some users.[5][6]

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWikicontributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects

Stimulation - In terms of its effects on the user's physical energy levels, mephedrone is commonly considered to be extremely stimulating and energetic. This encourages activities such as running, climbing and dancing in a way that makes mephedrone a popular choice for musical events such as festivals and raves. The particular style of stimulation which mephedrone presents can be described as forced. This means that at higher dosages it becomes difficult or impossible to keep still, as jaw clenching, involuntarily bodily shakes and vibrations become present, resulting in an extreme unsteadiness of the hands and a general lack of motor control.

Spontaneous physical sensations - The "body high" of mephedrone can be described as a moderate to extremely euphoric tingling sensation that encompasses the entire body. It is capable of becoming overwhelmingly pleasurable at higher dosages. This sensation maintains a consistent presence that steadily rises with the onset and hits its limit once the peak has been reached.

Vibrating vision - A person's eyeballs may begin to spontaneously wiggle back and forth in a rapid motion, causing vision to become blurry and temporarily out of focus-- a condition known as nystagmus.

Dehydration - Dry mouth and dehydration are a universal experience with mephedrone and are a product of an increased heart rate and extreme motivation to engage in strenuous physical activities. While it is important to avoid becoming dehydrated, especially when out dancing in a hot environment, there is a potential possibility of suffering from water intoxication through over-drinking so it is advised that users simply sip at water and never over drink.

Difficulty urinating - Higher doses of mephedrone result in an overall difficulty when it comes to urination, an effect that is completely temporary and thought to be harmless.

Vasoconstriction - A survey conducted by the UK's National Addiction Centre reported that 15% of mephedrone users experienced cold or blue fingers and lips[7] indicative of vasoconstriction occurring.[8]

Body odor alteration - Mephedrone can potentially leave a very distinct and unpleasant odor within one's urine, sweat and general bodily secretions which is often described as smelling similar to cat urine.[9]

Teeth grinding - This component can be considered to be less intense when compared with that of MDMA.

Cognitive effects

The cognitive effects of mephedrone can be broken down into several components which progressively intensify proportional to dosage. The general head space of mephedrone is described by many as one of extreme mental stimulation and powerful euphoria. It contains a large number of typical stimulant cognitive effects.
The most prominent of these cognitive effects generally include:

Cognitive euphoria - Strong emotional euphoria and feelings of happiness are present within mephedrone and are likely a direct result of serotonin and dopamine release.

After effects

The effects which occur during the offset of a stimulant experience generally feel negative and uncomfortable in comparison to the effects which occurred during its peak. This is often referred to as a "comedown" and occurs because of neurotransmitter depletion. Its effects commonly include:

Toxicity and harm potential

Almost nothing is known about the long-term effects of mephedrone due to its short history of its use.[10] Along side of this, the exact toxic dosage is unknown.[11]

In 2010, unconfirmed reports speculated about the role mephedrone has played in the deaths of several young people in the UK. By July 2010, mephedrone had been alleged to be involved in 52 fatalities in the UK, but detected in only 38 of these cases. Of the nine that coroners had finished investigating, two were caused directly by mephedrone.[12] The first death reported to be caused by mephedrone use was that of 46-year-old[13] who had underlying health problems and repeatedly injected the drug.[14] A report in Forensic Science International in stated mephedrone intoxication has been recorded as the cause of death in two cases in Scotland.[15]

Despite similarities to known neurotoxins such as methamphetamine and other cathinone derivatives, mephedrone does not appear to produce neurotoxic effects in the dopamine system of mice.[16]

Tolerance and addiction potential

As with other stimulants, the chronic use of mephedrone can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.

Tolerance to many of the effects of mephedrone develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). Mephedrone presents cross-tolerance with all dopaminergicstimulants, meaning that after the consumption of mephedrone all stimulants will have a reduced effect.

Dangerous interactions

Although many psychoactive substances are safe to use on their own, they can become dangerous or even life-threatening when taken with other substances. The list below contains some potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses but still increase the possibility of injury of death. Independent research should always be conducted to ensure that a combination of two or more substances is safe before consumption.

Alcohol - Alcohol can be dangerous to combine with stimulants due to the risk of accidental over-intoxication. Stimulants mask the sedative effects of alcohol, which is the main factor people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects of alcohol are left unopposed, which can result in blackouts and respiratory depression. If combined, one should strictly limit themselves to only drinking a certain amount of alcohol per hour.

DXM - Combinations with DXM should be strictly avoided due to DXM's effects on serotonin and dopamine reuptake. This can lead to panic attacks, hypertensive crisis, or serotonin syndrome.

MXE - Combinations with MXE may dangerously elevate blood pressure and increase the risk of psychosis.

Tramadol - Tramadol lowers the seizure threshold.[17] Combinations with stimulants may further increase this risk.

MDMA - The neurotoxic effects of MDMA may be increased when combined with other stimulants.

Legal issues

European Union (EU): In October 2010, a European Union commission called for an EU-wide ban of mephedrone.[19]

Australia: Mephedrone has been added to the Australian federal drug watch list and is now considered illegal if intended for human consumption.

Austria: Mephedrone is illegal to possess, produce and sell under the SMG (Suchtmittelgesetz Österreich).

Belgium: Mephedrone was banned on April 29, 2010, by making it a regulated drug requiring the approval of the Ministry of Human Health to import, sell, or possess.

Brazil: Mephedrone was added to the list of Scheduled drugs (class F2), making it illegal to possess, sell, or manufacture without a license as of August 2011.[20]

China: Mephedrone was made a Category I psychotropic substance, making it illegal to sell, buy, import, export, and manufacture as of September 2010.

Denmark: Denmark's Minister for Health and Prevention Jakob Axel Nielsen banned mephedrone, flephedrone and ethylcathinone on December 18, 2008. As of July 1, 2012, Denmark also created a type of analogue law that would include cathinones like mephedrone[21]

Finland: Through the Medicines Act, mephedrone is classified as a "medicinal product", making it illegal to manufacture, import, possess, sell, or transfer it without a prescription.

France: French Ministry of Health decided in early June 2010 to add mephedrone to the list of illicit substances in the "Journal Officiel du 11 juin 2010".[22]

Germany (Deutschland): Mephedrone has been added to Anlage I starting Jan 22, 2010 and will then be controlled in Germany.[23]

Israel: In December 2007, mephedrone was added to Israel's list of controlled substances, making it illegal to buy, sell, or possess.[24]

Netherlands: In March, 2010, the Dutch Ministry of Health and the Medicines Authority IGZ informed the Ministry of Justice that they now consider mephedrone an unregulated medicine; sales and distribution of it are now prohibited.

Poland: On August 25, 2010, mephedrone was added to the list of controlled "psychotropic drugs" in the I-P group.[26]

Romania: Mephedrone was added to Romania's list of controlled substances in February 2010.[27]

Russia: Mephedrone is classified as List 1 in Russian Federation as of August 2010. This means it is illegal to manufacture, buy, possess, or distribute.[28]

Slovak Republic: Starting March 1, 2011 mephedrone is controlled in the Slovak Republic.[29]

Sweden: In Sweden, the drug is classified as a health hazard. A ban on mephedrone went into effect on December 15, 2008, making its sale illegal. Use of 4-methylmethcathinone is not explicitly illegal under this regulation.

United Kingdom - Mephedrone is a Class B drug in the United Kingdom as a result of the cathinone catch-all clause.[30]

USA: Mephedrone is currently a Schedule I drug in the United States. This means it is illegal to manufacture, buy, possess, or distribute (sell, trade or give) without a DEA license.